The primary objective of this grant has been the study on the damage to renal grafts inflicted by humoral antibodies. In previous years the role of transplantation antibodies in hyperacute rejection of renal grafts by man and experimental animals has been demonstrated and elucidated to a great extent. More recently, the role of humoral antibodies and circulating immune complexes (IC) in late deterioration of renal grafts has been investigated. On the basis of these studies, the destruction of the graft by de novo deposition of IC appears likely. We will continue the study on the appearance of IC in sera of human recipients of renal grafts and attempt to identify the antigens participating in the formation of circulating IC. In parallel, sections of rejected grafts will be investigated for de novo deposition of IC and here again the identification of the culprit antigen(s) will be explored. Studies on xenograft rejection will be resumed with the specific aim of developing procedure of neutralization of humoral xeno-antibodies presumably responsible for acute xenograft rejection. A variety of procedures developed in this laboratory will be employed and improved. This includes: mixed agglutination with cell cultures, mixed agglutination with artificial cell monolayers, cytolysis in agar gel, double diffusion in gel with particulate antigens, inhibition of anti-antibody (AA) by IC, dispersion of IC in excess of antigen as evaluated by the disappearance of AA-inhibitory capacity of circulating IC, and disapperance of immunofluorescent staining of IC deposited in tissues.